All references cited in this specification, and their references, are incorporated by reference herein in their entirety where appropriate for teachings of additional or alternative details, features, and/or technical background.
The invention relates to a medical device for implantation into vessels or luminal structures within the body. In one embodiment, the present invention relates to stents and synthetic grafts which are coated with a controlled-release matrix comprising a medicinal substance for direct delivery to the surrounding tissues, which may include a ligand attached thereto for capturing progenitor endothelial cells in the blood contacting surface of the device to form mature, functional, endothelium at site of injury. In particular, the polymer matrix/drug/ligand-coated devices such as stents are for use, for example, in therapy of diseases and conditions such as restenosis, artherosclerosis, and endoluminal reconstructive therapies.
Disclosed in embodiments herein is a novel tube-shaped expandable scaffold configured to fit within the vasculature, including the cardiovasculature, having a low, propensity for biological rejection. Such scaffold may consist of, or comprise, a bioabsorbable polymer composition or blend that effectuates a combination of mechanical properties balancing elasticity, rigidity and flexibility. The polymer composition may include a base material including a bioabsorbable polymer, copolymer, or terpolymer, and a copolymer or terpolymer additive. Advantageously the polymer may be selected to undergo enzymatic degradation and absorption. In particular, the composition may allow for a “soft” breakdown mechanism allowing for the breakdown of the component polymers to be less injurious to the surrounding tissue.
A persistent problem associated with the use of metallic devices such as stents is found in the formation of scar tissue coating of the vascularly located stent, the so-called process of restenosis. Many have concluded that the continued risk of stent thrombosis due to the permanent aspect of metal stents has not been overcome by coating of the metal with drugs intended to prevent such calamities. On the contrary, an increase in death rate has also been associated with a number of these coatings. Moreover, metallic and polymeric stents may prevent vascular lumen remodeling and expansion.
With respect to stents, stents may prevent the healing of tissue and reduce complement activation of the immune response. Stents have also been associated in some instances with a reduced inflammatory response and trauma upon break-up of an implant and/or its component materials. Conventional stents may also not provide a desired degree of flexibility in shape allowing for easier implantation, particularly into blood vessels.
The present inventors have recognized a need to develop medical devices such as stents and vascular synthetic grafts, manufactured from biocompatible, biodegradable bioabsorbable polymer blends as base polymer which are useful for the treatment of disease, in particular of the vascular system. The medical devices may ameliorate problems associated with present devices.
As disclosed herein, it has been recognized by the present inventors that the base polymer may be selected to allow additional molecular free volume to encourage sufficient molecular motion so as to allow for re-crystallization to occur at physiological conditions (e.g., upon the addition of molecular strain). Increased molecular free volume may allow for an increase in the rate of water uptake adding both a plasticizing effect as well as increasing the bulk degradation kinetics.
In embodiments herewith, the compositions allow for a “soft” breakdown mechanism such that the breakdown proceeds while being friendly to the surrounding tissue (less inflammatory response, and rendering lower potential for trauma upon break up of an implant). By selecting a polymer or copolymer having an enhanced hydrophilic property for either the base or the additive or both, the polymer blend may reduce complement activation and minimize or prevent opsonization.
In certain embodiments, the bioabsorbable scaffolds allow flexibility and stretchability suitable for the implantation in the pulse movements, contractions and relaxations of, for example, the cardiovascular system.